DESCRIPTION (applicant's abstract): Our goal under this SBIR is to demonstrate the feasibility of using a novel Artificial Sequence-based Protein REceptor (ASPIRE) for the creation of a "protein chip." The development of new protein separation technology is essential to bridge the gap between genomics and rational disease diagnostics and treatment. Preliminary results indicate that we can design an artificial receptor, based solely on the predicted protein sequence, capable of purifying a target protein from a cell lysate. To prove that such a receptor will be useful for large-scale high-throughput proteome separation and analysis, we plan to 1) demonstrate that the technology is applicable to 6-10 representative proof of principle proteins; 2) optimize the critical receptor properties for efficient separation of complex samples; and 3) create an array of receptors capable of separating labeled proteins. Our data indicate that a chip based on the ASPIRE technology will be roughly 250x faster and lOx more sensitive than two-dimensional gel electrophoresis paired with mass spectrometry. In addition to the analysis of protein expression patterns, ASPIRE protein chips will allow researchers to conduct large-scale parallel analysis of posttranslational modifications and intracellular trafficking control much of cell regulation. We expect that this technology will have far-reaching implications for basic research, drug development, and disease diagnosis. PROPOSED COMMERCIAL APPLICATION: The market for proteomics is estimated at $4 billion and is rapidly growing. A protein chip enabling proteomics would allow for 1) rapid identification of molecular causes of disease and therapeutic targets 2) efficient screening of small molecules for therapeutic efficacy and toxicity, and 3) rational diagnostic and treatment strategies based on individual molecular profiling.